Tag Archives: apoptosis

Metabolic changes in living cells under electromagnetic radiation of mobile communication systems

I. L. Yakymenko1,2, E. P. Sidorik1, O. S. Tsybulin2

1R.E.Kavetsty Institute of Experimental Pathology, Oncology
and Radiobiology, National Academy of Sciences of Ukraine, Kyiv;
2Bila Tserkva National Agrarian University, Ukraine;
e-mail: iyakymen@gmail.com

Review is devoted to the analysis of biological effects of microwaves. The results of last years’ researches indicated the potential risks of long-term low-level microwaves exposure for human health. The analysis of metabolic changes in living cells under the exposure of microwaves from mobile communication systems indicates that this factor is stressful for cells. Among the reproducible effects of low-level microwave radiation are overexpression of heat shock proteins, an increase of reactive oxygen species level, an increase of intracellular Ca2+, damage of DNA, inhibition of DNA reparation, and induction of apoptosis. Extracellular-signal-regulated kinases ERK and stress-related kinases p38MAPK are involved in metabolic changes. Analysis of current data suggests that the concept of exceptionally thermal mechanism of biological effects of microwaves is not correct. In turn, this raises the question of the need to revaluation of modern electromagnetic standards based on thermal effects of non-ionizing radiation on biological systems.

Folate-related processes in human placenta: gene expression, aminothiols, proliferation and apoptosis

M. Yu. Obolenskaya, R. R. Rodriges, O. P. Martsenyuk

Institute of Molecular Biology and Genetic, National Academy of Sciences of Ukraine, Kyiv;
e-mail: m.obolenska@gmail.com

The paper contains short information concerning the role of folate-related processes in cell metabolism and multiple diseases which are characterized by hyperhomocysteinemia. The authors represent more detailed information about the folate-related processes in human placenta, namely about the content of aminothiols at different allelic variants of placental methylenetetrahydrofolate reductase during the course of physiological pregnancy and preeclampsia. The existing data concerning the expression and catalytic activi­ty of corresponding enzymes are corroborated by the authors’ own results that proved for the first time the functional activity of transsulfuration pathway in human placenta. This pathway is activated in placental explants in parallel with down-regulation of proliferation and up-regulation of apoptosis when hyperhomocystei­nemia is imitated by high concentration of homocysteine in culture medium. On the whole the presented data point to the importance of placental folate-related processes for its normal function.

Effects of α-tocopherol and its anologues on rat thymocytes programmed death induced by protein kinase inhibitors

G. V. Petrova, N. V. Delemenchuk, G. V. Donchenko

Palladin Institute of Вiochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: petrova@biochem.kiev.ua

It is established that α-tocopherol (α-ТPh) shows cytoprotective effect at the induction of rats’ thymocytes apoptosis by endocellular protein kinase inhibitors – staurosporine and phorbol ether in high concentration, and also on necrosis of the cells caused by sphyngosine. The effect of α-ТPh on thymocytes death caused by protein phosphatase type 2А inhibitor ocadaic acid is much less expressed. The obtained data testify that the known ability of α-ТPh to the inhibition of PKC and to the activation of protein phosphatase type 2А is not the main mechanism of its cytoprotective action. Partial reproduction of α-ТPh effects by its analogue α-tocopheryl acetate which is not capable to enter in redox reactions, and the absence of influence on the studied processes of an antioxidant of N-acetyl-L-cysteine do not confirm the antioxidant mechanism of α-ТPh action in this case. The inhibition by α-ТPh of the release of cytochrome c in the cytosol of cells testifies to the implementation of its cytoprotective effect at the level of mitochondrial membranes. We assume the existence of the universal mechanism of α-ТPh cytoprotective action that does not depend on the nature of apoptogenes and realized on the general for the majority of them stage of the cells death induction. The prevention by α-ТPh of mitochondria dysfunction by stabilizing mitochondrial membranes and reduction of their permeabilization is supposed as that.

Photoactivated fullerene C(60) induces store-operated Ca(2+) entry and cytochrome c release in Jurkat cells

S. M. Grebinyk1, K. O. Palyvoda2, S. V. Prylutska1, I. I. Grynyuk1,
A. A. Samoylenko2, L. B. Drobot2, O. P. Matyshevska1

1Taras Shevchenko Kyiv National University, Ukraine;
2Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: matysh@yahoo.com

The values of endoplasmic reticulum Ca2+-pool and store-operated Ca2+ entry (SOCE) were estimated in rat thymocytes and Jurkat cells loaded with indo-1 and treated with thapsigargin. It was shown that the relative value of SOCE in thymocytes was substantially lower than in Jurkat cells. Significant increase of SOCE in Jurkat cells preincubated with 10-5 M C60 and exposed to uv/visible light irradiation was detected at 1-3 h after exposure. At this time FCCP-induced Ca2+-release from mitochondria was shown to be reduced, while cytochrome c level into the cytoplasm of Jurkat cells, detected by Western blot analysis, to be increased. It is supposed that Ca2+ flux remodulation induced by photoexcited fullerene C60 in Jurkat cells might be involved in the initiation of signalling events leading to cell apoptosis.

Effect of N-stearoylethanolamine on the DNA fragmentation intensity in tumour and extratumoral tissues of the human adrenal cortex

N. I. Levchuk1, V. M. Pushkarev1, O. I. Kovzun1,
A. S. Mikosha1, N. M. Gula2, M. D. Tronko1

1State Institution V. P. Komisarenko Institute of Endocrinology and Metabolism,
National Academy of Medical Sciences of Ukraine, Kyiv;
2Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: levnataly@meta.ua

The effect of different concentrations of N-stearoylethanolamine (NSE 18:0) on fragmentation of DNA in the tumoural and extratumour tissues of the adrenal glands in vitro was studied. In this work the following types of tissue were investigated­: extratumoural tissue from patients with hormonally active tumours, benign tumour tissue (hormonally active and hormonally inactive), tissue of malignant tumours and hyperplasic tissue of the adrenal glands (Itsenko-Cushing disease). It has been established that the NSE increases the intensity of DNA fragmentation only in the tissue of hormonally inactive tumours. Benign hormonally active tumours, malignant tumours and hyperplastic tissue of the adrenal glands were resistant to the NSE. The possible mechanisms of resistance to the drug are discussed.

Rhamnazin inhibits proliferation and induces apoptosis of human jurkat leukemia cells in vitro

А. А. Philchenkov, М. P. Zavelevych

R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology,
National Academy of Sciences of Ukraine, Kyiv;
e-mail: apoclub@i.ua

Antiproliferative and apoptogenic effects of rhamnazin, a dimethoxylated derivative of quercetin, were studied in human acute lymphoblastic leukemia Jurkat cells. The cytotoxicity and apoptogenic activity of rhamnazin in vitro are inferior to that of quercetin. The apoptogenic activity of rhamnazin is realized via mitochondrial pathway and associated with activation of caspase-9 and -3. The additive apoptogenic effect of rhamnazin and suboptimal doses of etoposide, a DNA topoisomerase II inhibitor, is demonstrated. Therefore, methylation of quercetin modifies its biological effects considerably.

Biological effects of thyroid hormones

T. S. Saatov, A. A. Abduavaliev

Institute of Bioorganic Chemistry, Uzbekistan Academy of Sciences, Tashkent;
e-mail: t.saatov@yandex.ru

The article presents the findings from the study on multifunctional effects of thyroid hormones in relation to normal and malignantly transformed tissues and cells. Both “rapid” and «slow» effects of thyroid hormones including calorigenic effects and effects over adenylate cyclase – cAMP system have been described.  Thyroxin (Т4) has been established capable to inhibit proliferation and to induce apoptosis of cells carrying Т4 receptors on their membranes as well as to change course of metabolic processes under its effect. Spectrum of Т4 targets is quite broad to include not only cells of hormone-producing organs, to name those of the breast and the colon, but also other types of cells to name melanin-containing ones; Т4 effects resulting in reconstruction of presentation of regulatory proteins on the cell membrane surface to ultimately activate the process of cell apoptosis.  Our findings help determine alternative paths for hormonal regulation of cell proliferation and apoptosis of cells of hormone-dependent tumors, breast cancer, in particular, upon impossibility to regulate the processes by conventional methods. This facilitates understanding mechanisms for activation of signal system of the breast cancer’s cells by hormones upon changes in expression of receptors on the cells’ surface, making possible development of novel strategy for replacement therapy of hormone-dependent tumors upon low efficacy of drug therapy.

Sweet taste of cell death: role of carbohydrate recognition systems

R. Bilyy, R. Stoika

Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv;
e-mail: r.bilyy@nas.gov.ua; stoika@cellbiol.lviv.ua

This paper describes a complicated way how the glycoepitops’ alterations on a surface of dying cells allow investigators to decipher specific mechanisms underlying cell restructuring at apoptosis. These glycoepitops are important at removal of fragments of dying cells from the body, which can be a cause of formation of the auto-antibodies.

Manifestations of oxidative stress and molecular damages in ovarian cancer tissue

H. I. Falfushynska1,2, L. L. Gnatyshyna1,2, H. V. Deneha1, O. Y. Osadchuk1, O. B. Stoliar1

1Volodymyr Hnatiuk Ternopil National Pedagogical University, Ukraine;
e-mail: halynka.f@gmail.com;
2I.Ya. Horbachevsky Ternopil State Medical University, Ukraine

Indices of oxidative stress are recognized molecular markers and prognostic criteria for malignant transformation of tissue, but their value depends on the type of tumor and the stage of its development. The goal of this study was to clarify the relationship between the characteristics of the oxidative stress system including­ metal-associated ones and the cytotoxicity manifestations in neoplastically transformed human ovarian tissue. The highest level of Mn-superoxide dismutase activity (by 630%) and metallothionein protein (MT, 100%) has been estimated for the first time in malignant ovarian tissue compared to normal ovarian tissue. The researchers have also found a much higher level of oxy-radical formation (by 332%), a lower activity of catalase (by 49%) and a lower level of reduced glutathione (by 46%) and its redox index (0.84 versus 0.89 in the control) in tumor tissue. Under the relatively stable content of zinc, copper and cadmium in MTs, the content of zinc and especially copper in a form non-binding with MTs was significantly lower in the malignant tissue compared to normal one while the content of cadmium was higher. A discriminant analysis of all definable parameters revealed that the higher content of the products of oxidative destruction of proteins, lipids, fragmented DNA and the activity of cathepsin D, especially in its free form (by 235%), are the main characteristic signs of malignant ovarian tissue.

The role of reactive oxygen species in tumor cells apoptosis induced by landomycin A

L. V. Lehka1, R. R. Panchuk1, W. Berger2, Ju. Rohr3, R. S. Stoika1

1Institute of Cell Biology, National Academy of Sciences of Ukraine, Lviv;
2Institute of Cancer Research, Medical University of Vienna, Austria;
3Department of Pharmaceutical Sciences, University of Kentucky, USA;
e-mail: lilyalehka@gmail.com

Landomycin A (LA) is a new antitumor antibiotic of angucycline group, possessing high antitumor activity against cancer cells of different origin, which induces early apoptosis in target cells. It was shown that under LA action the level of reactive oxygen species (ROS) in human T-leukemia cells had increased 5.6 times in comparison to control already at the 1st hour after the addition of studied antibiotic to the culture medium. At the 6th hour after incubation of cells with LA the nucleosomal DNA cleavage, chromatin condensation and nucleus fragmentation were observed, indicating apoptotic cell death. Catalase (scavenger of hydrogen peroxide), mannitol (scavenger of hydroxyl radicals) and superoxide dismutase (scavenger of superoxide radicals) reduced the level of ROS production under LA, suggesting the generation of H2O2, OH and O2 radicals, respectively. It was revealed that catalase and mannitol effectively inhibited LA-mediated tumor cell death, increasing 2.5 times the percentage of alive cells in comparison to LA. However, superoxide dismutase had no significant inhibitory effect on cytotoxic activity of LA, indicating the minor role of superoxide anions in the implementation of antitumor activity of this antibiotic. Combination of catalase, mannitol and superoxide dismutase with LA increased 4-fold the percentage of alive cells in comparison to the action of LA. Dynamics of ROS formation confirms that the increase of ROS is a very rapid process, but at the same time it is not a direct consequence of apoptosis triggering, mediated by mitochondria.